The objective of this research is to devise an in vivo model system that permits the study of the interaction of tumor viruses (SV40 and RNA tumor viruses) with the cells of an organism of various stages of differentiation under highly defined conditions. Explanted mouse blastocysts were microinjected with purified SV40 DNA. After surgical transfer to the uteri of pseudopregnant surrogate mothers, approximately 40% of the blastocysts developed to term and became healthy adults without apparent tumors at one year of age. Molecular hybridization tests for the presence of SV40 specific DNA sequences were conducted on DNA extracted from various organs of these animals. Between 0.5 and 13 SV40 genome equivalents per diploid mouse equivalent were found in some organs of 40% of the adult survivors. These results are consistent with the working hypothesis that SV40 DNA may have been integrated into the host genome.